The present invention relates to adhesive materials, and particularly to a new group of dermatologically acceptable, moisture vapor-permeable, pressure-sensitive adhesive compositions which can be used in various medical contexts, including as a component of a wound dressing.
Wound management has developed rapidly in recent years due to advances in the understanding of the wound healing process and to the advent of new materials and techniques for use in wound dressings. In particular, much activity has occurred in the development of pressure-sensitive adhesive, moisture vapor-permeable wound dressings. These wound dressings provide coverings that protect wounds from further harm, enhance the natural healing process, and prevent bacterial invasion. Despite the availability of these newly-developed materials, infection is still a common complication associated with conventional dressings.
A wound is a loss of continuity of skin or mucous membrane due to accidental injury or planned surgery. Wound healing is essentially the replacement of dead or damaged tissue by healthy, living cells. Healing can occur either by partial or complete regeneration or by repair. Regeneration implies complete restitution to regain the original tissue structure. Repair, on the other hand, involves formation of a new permanent structure, a scar. Wound healing is typically a two-step process, involving regeneration of epithelial tissue and repair of connective tissue.
Among the various factors which affect wound healing are, for example, host resistance, environment and location of the wound, and the presence of bacteria. The patient's overall health, metabolic and nutritional status determine resistance. Blood flow, lymphatic drainage, temperature and humidity are important in respect of the environment and location of a wound. Bacteria at the wound site can proliferate and cause infection.
Wound dressings should possess a number of important characteristics in order to protect the wound and enhance its ability to heal. An ideal wound dressing should (i) have optimal water permeability to prevent desiccation of the wound and fluid accumulation under the covering; (ii) prevent microbial invasion from the environment; (iii) have no antigenic properties; (iv) be an elastic-plastic film to facilitate intimate covering of all possible contours of the human body; (v) be capable of both adhering well to the wound and being readily removable without causing any damage to the tissue beneath the covering; and (vi) be inexpensive to produce and readily amenable to storage.
Modern wound dressings are generally constructed of a backing sheet with a pressure-sensitive adhesive on one side. The backing sheet is typically moisture vapor permeable, allowing water vapor to escape from the wound site while preventing liquid water from entering or escaping from the site. In addition, bacteria are prevented from passing through the wound dressing. The adhesive provides the desired pressure-sensitive adherence for securing the backing to the wound site and retaining the backing in the desired position.
High moisture vapor-permeability of a dressing prevents maceration of the skin due to occlusion of transepidermal fluid lost from the body and delamination of the dressing from the wound site, as will be explained below. Many modern wound dressings are known for their high moisture vapor-permeability, as measured by the moisture vapor transmission rate (MVTR). For example, U.S. Pat. Nos. 4,340,043 and 4,360,369 disclose an adhesive-coated, polymeric sheet material having a high MVTR. This material is commercially available as a wound dressing marketed, under the mark Op-Site.RTM., by Nephew & Smith, Ltd. See also U.S. Pat. No. 4,233,969.
The moisture permeability of such dressings is a function of the moisture permeability of both the polymeric film and the pressure-sensitive adhesive used. Many wound dressings use moisture permeable adhesives. For example, U.S. Pat. No. 3,645,835 (Hodgson) discloses both a moisture vapor-permeable backing material and a moisture vapor-permeable pressure-sensitive adhesive. The Hodgson patent also teaches that both the backing material and adhesive are unaffected by water, i.e., they neither swell nor absorb water. U.S. Pat. Re. No. 31,887, a reissue of the Hodgson patent, specifically discloses the backing material as a polyurethane and the adhesives as a polyvinyl ethyl esters or an acrylate. See also U.S. Pat. No. 4,638,797.
Polyurethane adhesives have been developed which are suitable for wound dressings. For example, U.S. Pat. No. 3,796,678 discloses a polyurethane adhesive which is highly branched and isocyanate-blocked with monofunctional alcohols. U.S. Pat. No. 4,626,475 relates to a polyurethane having improved adhesive properties, accomplished by using a bicyclic amide acetal additive. Aqueous-based polyurethane adhesives have also been developed. See, for example, U.S. Pat. Nos. 4,442,259 and 4,507,430. As explained above, the overall goal of wound dressings is to prevent infection and to provide an environment that promotes wound healing. To prevent infections, modern wound dressings are continuous, or occlusive, that is, there are no openings in the dressing through which bacteria from the environment can reach the wound site. Even with an occlusive dressing, however, infection may occur at the wound site if the dressing loses its integrity or if bacteria are already present at the wound site or the surrounding skin. Loss of integrity allows microbes from the environment to reach the wound site and cause infection. Bacteria already present at a wound site can also proliferate and cause infection.
The principle cause of integrity failure of an occlusive film dressing is delamination of the dressing from the wound site. Delamination is a function of the moisture permeability of the dressing and the ability of the dressing to absorb fluid. If the dressing does not have a high enough MVTR, then fluid from the wound or surrounding skin can accumulate. If the pressure-sensitive adhesive used neither absorbs this fluid nor allows it to reach an absorbent layer, then delamination between the pressure-sensitive adhesive and the wound site and/or surrounding skin will occur. If the delamination reaches the edge of the dressing, loss of dressing integrity results in the wound site being exposed to environmental microbes, i.e., loss of the bacterial barrier. The integrity of a dressing thus, is a function of both its moisture vapor permeability and fluid swellability. One of the major problems with current wound dressings is the use of materials with an insufficiently high MVTR to avoid delamination and pressure-sensitive adhesives unable to absorb fluid.
Attempts have been made to develop water-swellable adhesives by incorporating various substances into the adhesive which absorb water. Most of these attempts utilize gel adhesives. For example, U.S. Pat. No. 4,661,099 discloses a water-absorptive polyurethane gel adhesive wherein polyols are immobilized in the cross-linked polyurethane. U.S. Pat. No. 4,367,732 relates to a polystyrene-based gel adhesive in which water-swellable hydrocolloids are dispersed. See also U.S. Pat. No. 3,648,835 and Re. No. 31,887. Upon absorbing water, such gels tend themselves to dissolve in the water. Gel adhesives generally lack the inherent stability and storage convenience of solid adhesives. See also U.S. Pat. Nos. 4,233,969, 4,156,066 and 4,156,067, directed to polyurethane films that are water-swellable.
Even if a dressing maintains integrity, the enclosed environment provided by dressings may allow bacteria present at the wound site on the surrounding skin to multiply unduly and lead to infection. Numerous bacteria are present on human skin. Some may survive an initial application of a topical antimicrobial agent and act as seeds for subsequent growth. Continuous application of an antimicrobial agent would be highly desirable.
Recently, several wound dressings have been developed wherein an antimicrobial agent is applied or added to the polymeric film or, more preferably, to the adhesive. For example, U.S. Pat. Nos. 4,554,317 and 4,643,180 disclose application of an agent to the surface of a membrane or adhesive, respectively. Other attempts have been directed to the formation of a chemical complex between the antimicrobial agent and the film or adhesive. U.S. Pat. Nos. 4,542,012 and 4,323,557 teach complexing iodine with polyvinylpyrrolidone residues in polymer. Release of the antimicrobial agent depends, however, on its appropriate dissociation from the chemical complex.
Still other prior art dressings teach a physical combination of the antimicrobial agent and polymer or adhesive. For example, U.S. Pat. No. 4,614,787 discloses a pharmacologically active agent dispersed through a cured polymeric film to which an adhesive may be applied. U.S. Pat. No. 4,310,509 discloses a flexible-backing material to which is applied a composition of a broad-spectrum antimicrobial agent homogeneously and stably dispersed in a pressure-sensitive adhesive. U.S. Pat. No. 4,460,369 discloses an adhesive-coated, liquid-impervious, moisture vapor-permeable, thin polymer sheet in which a solid antibacterial material in a finely divided form is incorporated within the adhesive. U.S. Pat. Nos. 4,156,066 and 4,156,067 disclose that a medicament may be added to a lactone-modified polyurethane which is applied to the skin as a film. See also U.S. Pat. Nos. 3,896,789 and 3,769,071, which disclose addition of other bioactive agents, such as retinoic acid and 5-fluorouracil, to a polyurethane adhesive.
A problem inherent in these prior art attempts is that since most adhesives are not water-soluble, water-soluble antimicrobials may only exist as a separate phase dispersed throughout the adhesive. For example, the Berglund Pat. discloses that if an antimicrobial is water-soluble and is in a water solution, a stable water-in-oil emulsion is formed upon mixing with the adhesive. If, on the other hand, an antimicrobial is soluble in an organic solvent and is in solution in that solvent, and the organic solvent is miscible with the adhesive solution, then the solvent of the adhesive extracts the solvent of the antimicrobial solution, causing the antimicrobial to separate out as distinct, minute, separate phase particles.
Still another approach utilizes adhesives in which the bioactive agent can be truly dissolved in the adhesive. For example, U.S. Pat. Nos. 4,307,717 and 4,675,009, both issued to Hymes et al., disclose a flexible backing material provided with a hydrophilic, adhesive matrix which has a solid phase of a polysaccharide and a liquid phase of an alcohol, carbohydrate and/or protein, where a medicinal agent is "molecularly dispersed," rather than encapsulated, in the matrix. The Hymes '009 Pat. is a continuation-in-part of the '717 Pat. and states that the adhesive is capable of absorbing moisture and that the medicinal agent is "molecularly dissolved and/or suspended" in the adhesive matrix.
Despite recognition of the many practical wound dressing design problems, proper solution to all these problems in a single wound dressing has not been demonstrated in the prior art. Despite improvements in modern wound dressings, dressing materials are needed that comprise higher-MVTR compositions and pressure-sensitive adhesives. The MVTR of a pressure-sensitive adhesive is usually the limiting factor in the total moisture permeability of a film-backed dressing. Moreover, even though adhesives should optimally absorb or transport fluid, nearly all medically suitable, pressure-sensitive adhesives which are currently available are unaffected by water, i.e, they neither swell nor absorb water.
While effective to some degree, conventional wound dressings which incorporate drugs and other bioactive agents in a pressure-sensitive adhesive layer are generally limited to solvent-based (rather than aqueous-based) antimicrobial agents or drugs, since most pressure-sensitive adhesives are hydrophobic. When water-soluble agents are placed within these adhesive systems, water-in-oil emulsions form or the agents precipitate out as solid particles. Release of the agent requires diffusion of particulates through a hydrophobic matrix.